Having completed over a decade on antiviral treatment of genital herpes, we turned to studies of disease prevention and immunotherapy. In the first years of this project we completed a series of open and blinded Phase-1 and 2 studies of multiple generations of candidate vaccines containing recombinant HSV-2 glycoprotein D and B in alum or MF-59 lipid emulsion. We documented excellent primary and boosted immune responses and safety of the vaccine candidates. In the past year, we completed and are reporting two major Phase-III clinical studies. The first is a two center study in which a vaccine was given to 202 patients with frequently occurring genital herpes to determine whether the rates of recurrence and disease severity would be reduced by immunotherapeutic vaccination. That study succeeded in showing a reduction in disease severity but not in recurrence frequency. More recently we unblinded a multiple center study of primary vaccinations for prevention of genital herpes in seronegative partners of individuals with proven infection. This study showed no efficacy. Vaccine studies are now halted pending the availability of new vaccine candidates.